LOUISVILLE, Ky. — When Joseph Grimaldi
suffered a relapse of a childhood bone cancer and needed a stem-cell
transplant, he stood on principle.

“I told the doctor there was no
way I would be treated with embryonic cells,” the Florida teenager recounted. “My principles
and my faith come before my health.”

Unfortunately, his own body didn’t
produce enough adult stem cells for a successful transplant. He and his family
are hoping that chemotherapy has finally knocked out all traces of his Ewing’s sarcoma.

If research with human embryonic
stem-cell research finds cures, millions of Americans may face a dilemma
similar to Grimaldi’s. Will patients be forced to
choose between standing on principle and suffering on the one hand and
undergoing treatments derived from human embryos denied a chance to develop and
grow toward birth on the other?

A human embryo is a unique boy or
girl from conception to eight weeks, with DNA, life-expectancy — and the right
to life.

Stem cells are cells in the bone
marrow that have the ability both to multiply and to differentiate into
specific blood cells and other cell/tissue types. This ability allows them to
replace cells that have died, and they have been used to replace defective
cells and tissues.

Embryonic stem-cell research,
which involves the killing of a unique human being, has proven not only
destructive and costly, but has not produced a cure. Adult stem-cell research,
which uses cells from adult tissues or umbilical cords, does not require the
destruction of human life. It has proven successful in treating different kinds
of cancers and autoimmune diseases such as multiple sclerosis.

Pope John Paul II said that all
research using stem cells from human embryos is “morally unacceptable.”

In his 1995 encyclical Evangelium Vitae (The Gospel of Life), John Paul
said, “This moral condemnation also regards procedures that exploit living
human embryos and fetuses — sometimes ‘produced’ for this purpose by in vitro
fertilization — either to be used as ‘biological material’ or as providers or
organs or tissue for transplants in the treatment of certain diseases.

“The killing of innocent human
creatures, even if carried out to help others, constitutes an absolutely
unacceptable act.”

President Bush’s July 19 veto of
federal funding for human embryonic stem-cell research laid the matter to rest
— for a while. While research advocates are not resting, a new discovery
promises to sidestep the ethical debate.

A team of scientists from the University of Louisville’s
JamesGrahamBrownCancerCenter
stem-cell biology program, led by Dr. Mariusz Ratajczak, have isolated some tiny cells in mouse bone
marrow that act indistinguishably from embryonic cells. They have successfully
cultured marrow cells, once thought to be useful only for renewing blood cells,
into the major tissue types, including brain, nerve, heart muscle and
pancreatic cells.

The results, published in the
scientific journal Leukemia in
February, raised hopes that similar results can be done with human cells.
Successes with human cells are now being reported.

These cells, called Very Small
Embryonic Like cells or VSELs, behave exactly like
embryonic cells, but, since they do not require the destruction of an embryo,
their use is morally acceptable.

Ratajczak’s training as a hematologist and
oncologist — studying diseases
of the blood with a focus on leukemia — led him to believe that there were
cells in adult human bone marrow that had not been fully characterized from the
standpoint of their scientific and medical potential.

‘Newborn’ Cells

Bone marrow and umbilical cord blood are known to contain
what are called hematopoietic (blood-making) stem
cells. They are useful in treating blood diseases like leukemia. Nobody had ever taken a close look
at the entire population of bone marrow/cord blood cells to determine exactly
what the mechanism is that helps
treat these diseases; they just assumed it was a mechanism of the blood-making
cells.

“In all of these deliberations concerning stem-cell
plasticity, the concept that (bone marrow) may contain heterogeneous
populations of stem cells was surprisingly not taken carefully enough into
consideration,” Ratajczak told
the Register. “We postulated that the presence of heterogeneous
populations of stem cells in [bone marrow] tissue should be considered first. …
This led us to the identification of very small embryonic-like stem cells in
the adult bone marrow tissue.”

He is guardedly optimistic that his VSELs may be just as good as embryonic stem cells for
research.

“These cells could be an alternative, but today we do not
have enough data to tell which cells from ‘the biological’ point of view would
perform better as a source of cells for regeneration,” he said. “What I can
tell you today is this: that our preliminary data suggest that these cells will
be very similar in their biological potency.”

His study garnered an Editor’s
Choice award from Nature Publishing Group, which is
responsible for 65 scientific journals. Since then, Ratajczak’s
team has seen its own results confirmed and duplicated in five laboratories,
including Mount Sinai School of Medicine in New York,
and the University
of Illinois, where
scientists have isolated similar cells in human cord blood samples. The Illinois group presented their results at
the annual meeting of the International Society of Stem Cell Researchers, which
was held June 17-21 in Toronto.

“The confirmation is extremely promising,” says Dr.
Gerry Sotomayor, director of the Babies for Life
Foundation in Atlanta,
which promotes umbilical cord blood donation for stem cell transplants. “We met
with Dr. Ratajczak in March, and since then we have
been sending him human cord blood samples. He has been able to isolate VSEL
cells in humans, and we hope to form the major tissue types from them.”

If the results pan out, so-called adult stem cells
(some have begun to call them “newborn stem cells”) may turn out to be as pluripotent (capable of producing many tissue types) as
embryonic cells, which is exactly why many in the scientific community have
insisted on the latter.

No Rejection

An advantage VSELs would
hold over embryonic cells is that they can come from the patient, and thus
avoid the danger of rejection which donated cells incur. Still, they may share
the problem that embryonic cells have had until now: They are difficult to
control, and can develop into a tissue type other than the one intended,
causing cancerous tumors called terratomas. Though
acknowledging the difficulty, Ratajczak remains
hopeful and confident in his Louisville
team.

“Currently, we are working on developing appropriate
strategies to differentiate these cells derived from the VSELs-derived
clusters into tissue-specific cells that will not grow terratomas
in mice,” he said

VSEL cells may be just the kind of
“embryonic-type” cells that a member of the President’s
Council on Bioethics advocated in May 2005.

“I support the council’s efforts
to identify means of obtaining human pluripotent stem
cells for biomedical research that do not involve killing or harming human
embryos and do not invite the exploitation of women to obtain ova,” Robert
George of PrincetonUniversity said at the
time. “If such means can be identified, research involving embryonic or
embryonic-type stem cells could go forward, and be funded by the federal
government, without ethical qualms and controversy.”

Sotomayor, of the Babies for Life Foundation, said that not
only cord blood, but placenta and other tissues resulting from human birth are
particularly rich in VSEL cells.

“We are debating about federal funds for embryonic
cells that require the destruction of life, yet we throw away something
morphologically and functionally identical every day,” he said.

His foundation is pushing for the “universal
collection” of these tissues after every birth. “Doing it for every birth will
result in a public resource of great genetic diversity,” said Sotomayor, who recently left his OB/GYN practice to fully
dedicate himself to research and postnatal tissue collection.

In April, Georgia Gov. Sonny Perdue signed an executive order creating
the Governor’s Commission for Newborn Umbilical Cord Blood Research and Medical
Treatment. The commission will establish a network of postnatal tissue and
fluid banks in partnership with universities, hospitals, nonprofit
organizations and private firms in Georgia for the purpose of
collecting and storing postnatal tissue and fluid. Until now, cord blood banks
have been a private matter.

Stem-cell transplants from cord
blood have a 50%-60% success rate. One private laboratory, however, Stemcyte in Arcadia,
Calif., boasts an 85%-90% success
rate. Sotomayor hypothesizes that VSEL cells may hold
the key to the higher rate.

“In most laboratories, the samples
are subjected to a cleansing process. Stemcyte, while
treating the samples with utmost care, doesn’t put them through the wash,” he
said. “The tiny VSEL cells are lost in many samples in other labs. They must
aid the transplant in ways we are just beginning to understand.”

Ratajczak concurred, explaining that the VSELs are a support for the transplant’s “take” or
“engraftment,” and added, “This would be in particular important for hematopoietic transplants performed with human cord blood.”

More Data Needed

Dr. Hans-Willem Snoeck of
Mount Sinai School of Medicine’s Department of Gene and Cell Medicine, while
admitting that Ratajczak’s discovery is interesting,
added a word of caution. “The Mount Sinai lab
found different cells from those found by Dr. Ratajczak,
although they are also embryonic-like. It is very difficult to replicate
findings exactly at the adult stem cell level.”

He also told the Register that VSELs,
even when differentiated, are at this point different from embryonic cells.

“Calling them ‘functionally equivalent’ is a bit
misleading. Embryonic cells can be grown virtually ad infinitum and VSELs can’t be grown at all,” he said. “These cells have
been differentiated to have the markers of other tissue types, but that isn’t
the same thing as forming tissue types such as pancreatic cells that will
behave as such in a patient. Also, since these cells are only about .02% of
bone marrow cells, their value is very limited unless we develop technology to
grow them.

“Promising? Yes. Revolutionary? Not yet. Much more
data is still needed.”